Maguire Eithne Margaret, Xiao Qingzhong, Xu Qingbo
From the Centre for Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom (E.M.M., Q. Xiao); and Cardiovascular Division, King's College London BHF Centre, United Kingdom (Q. Xu).
Arterioscler Thromb Vasc Biol. 2017 Nov;37(11):2026-2037. doi: 10.1161/ATVBAHA.117.309196. Epub 2017 Aug 31.
Vascular smooth muscle cells (VSMCs) play a role in the development of vascular disease, for example, neointimal formation, arterial aneurysm, and Marfan syndrome caused by genetic mutations in VSMCs, but little is known about the mechanisms of the disease process. Advances in induced pluripotent stem cell technology have now made it possible to derive VSMCs from several different somatic cells using a selection of protocols. As such, researchers have set out to delineate key signaling processes involved in triggering VSMC gene expression to grasp the extent of gene regulatory networks involved in phenotype commitment. This technology has also paved the way for investigations into diseases affecting VSMC behavior and function, which may be treatable once an identifiable culprit molecule or gene has been repaired. Moreover, induced pluripotent stem cell-derived VSMCs are also being considered for their use in tissue-engineered blood vessels as they may prove more beneficial than using autologous vessels. Finally, while several issues remains to be clarified before induced pluripotent stem cell-derived VSMCs can become used in regenerative medicine, they do offer both clinicians and researchers hope for both treating and understanding vascular disease. In this review, we aim to update the recent progress on VSMC generation from stem cells and the underlying molecular mechanisms of VSMC differentiation. We will also explore how the use of induced pluripotent stem cell-derived VSMCs has changed the game for regenerative medicine by offering new therapeutic avenues to clinicians, as well as providing researchers with a new platform for modeling of vascular disease.
血管平滑肌细胞(VSMCs)在血管疾病的发展中起作用,例如新生内膜形成、动脉瘤以及由VSMCs基因突变引起的马凡综合征,但对于疾病过程的机制知之甚少。诱导多能干细胞技术的进展现在使得使用多种方案从几种不同的体细胞中获得VSMCs成为可能。因此,研究人员已着手描绘触发VSMC基因表达所涉及的关键信号传导过程,以了解参与表型确定的基因调控网络的程度。这项技术也为研究影响VSMC行为和功能的疾病铺平了道路,一旦确定了罪魁祸首分子或基因并进行修复,这些疾病可能是可治疗的。此外,诱导多能干细胞衍生的VSMCs也因其可用于组织工程血管而受到关注,因为它们可能比使用自体血管更有益。最后,虽然在诱导多能干细胞衍生的VSMCs可用于再生医学之前仍有几个问题有待澄清,但它们确实为临床医生和研究人员提供了治疗和理解血管疾病的希望。在这篇综述中,我们旨在更新干细胞生成VSMC的最新进展以及VSMC分化的潜在分子机制。我们还将探讨诱导多能干细胞衍生的VSMCs的使用如何通过为临床医生提供新的治疗途径以及为研究人员提供血管疾病建模的新平台,改变了再生医学的局面。